• Korean Journal of Clinical Pharmacy
• /
• v.11 no.2
• /
• pp.57-61
• /
• 2001

The effect of circadian rhythm on the pharmacokinetics of acebutolol was studied in rabbits administered intravenous 5 mg/kg dose of acebutolol at 09:00 in the morning (a.m) and 22:00 in the evening (p.m). A significant effect of circadian rhythm of pbarmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance (CLt), higher plasma concentration and the area under the plasma concentration time curve (AUC) when acebutolol was given in the evening. The plasma concentration of acebutolol was increased significantly (p<0.05) at 12-24 hr after dosing in the evening. The AUC was greater in the evening $(111\%)$ than that in the morning and $CL_t$, was higher when acebutolol was given in the morning ($1.12\pm0.24$ ml/hr) versus in the evening ($1.01\pm0.22$ ml/hr), but those were not significant. Therefore, It is reasonable to consider individual circadian rhythm for effective dosage regimen of acebutolol in clinical chronotherapeutics.

• YAKHAK HOEJI
• /
• v.34 no.6
• /
• pp.401-406
• /
• 1990

The Pharmacokinetics of furosemide (5 mg/kg iv) was investigated in rabbits with folate (75 mg/kg, 150 mg/kg 300 mg/ug, iv) induced renal failure. The plasma concentration was increased and urinary excretion was decreased significantly compared with those of normal rabbits. ${\alpha},\;{\beta}\;and\;K_{12},\;K_{21},\;K_{10}$ were decreased, $t_{1/2}$ and AUC were increased significantly. Correlation of serum creatinine concentration and AUC, renal clearance have linear relationship respectively. In short, dosage regimen of furosemide is considered to be adjusted in the dose size and the dosing interval by degree of serum creatinine concentration.

• YAKHAK HOEJI
• /
• v.35 no.1
• /
• pp.38-44
• /
• 1991

It has been reported that the pharmacokinetic behaviors of drugs which are mostly metabolized in the liver are significantly different in patients with renal failure. Theophylline(TP) is mainly metabolized in the liver (approximately 90%) and renal clearance of the drug is negligible (less than 10%). Therefore, we have investigated the changes in pharmacokinetics of theophylline in normal, G-ARF and U-ARF rats after an intravenous administration. The total body clearance of TP decreased approximately 40% in U-ARF rats. The reduced CL$_{T}$, value in U-ARF rats could be due to reduced hepatic intrinsic clearance by up to 40% since it has been published that plasma protein binding of TP and liver blood flow does not change in U-ARF rats.

• YAKHAK HOEJI
• /
• v.35 no.5
• /
• pp.379-383
• /
• 1991

This study was attempted to investgate the pharmacokinetics of theophylline (4 mg/kg i.v) in the rabbits pretreated with propranolol (1 and 2.5 mg/kg/hr, infusion) for four hours. The plasma concentration and AUC of theophylline were increased in rabbits pretreated with propranolol as compared with those of normal rabbits. The amount of cumulative urinary excretion and renal clearance and total body clearance were decreased in rabbits pretreated with propranolol as compared with those of normal rabbits. The apparent volume of distribution was slightly affected by change of the clearance of theophylline. From the results of this experiment, it is desirable that dosage regimen of theophylline should be adjusted when theophylline combined with propranolol in clinical pharmacy practice.

• Archives of Pharmacal Research
• /
• v.24 no.4
• /
• pp.338-341
• /
• 2001

Circadian variations of sulfamethoxazole pharmacokinetics were studied after a single oral administration of sulfamethoxazole, 50 mg/kg, to rabbits at 09:00 (a.m.) and 22 :00 (p.m.). The profiles of plasma sulfamethoxazole concentration showed from 6h to 24 h significant statistical difference (p<0.05) between 09:00 and 22:00. The half-life $t_{1/2} was significantly shorter in the morning (11.2 $\pm$3.2 h) when compared to the nighttime (15.4 $\pm$ 3.5h) (7< 0.05). The AUC was significantly decreased in the morning (1325 $\pm$ 264${u}g/ml$.h) than that in the nighttime (2059 $\pm$ 379${u}g/ml$. h) (p<0.05). Tota1 body clearance ($Cl_t$ was significantly higher when sulfamethoxazole was given in the morning (6.65 $\pm$ 0.23 ml/min) versus in the nighttime (4.28 $\pm$ 0.20 ml/min) (p<0.05).

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.155-156
• /
• 2003

RNA was isolated from mucosal tissue of the duodenum, jejunum, ileum and colon after perfusion. The gene expression profiles were measured using Affymetrix GeneChip(R) analysis. Prodrug valacyclovir permeability was 5-fold and 2-fold higher than the parent drug acyclovir in the jejunum and ileum, respectively.(omitted)

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.158-159
• /
• 2003

We have cloned and functionally expressed a sodium dependent human nucleoside transporter, hCNT2, from a CNS cancer cell line U251. Our cDNA clone of hCNT2 had the same predicted amino acid sequence as the previously cloned hCNT2 transporter. Of the several cell lines studied, the best hCNT2 transport function was obtained when transiently expressed in U251 cells.(omitted)

• Korean Journal of Clinical Pharmacy
• /
• v.9 no.1
• /
• pp.66-70
• /
• 1999

The effect of circadian rhythm on cyclosporine pharmacokinetics was studied in rabbits after oral administration of 10 mg/kg dose of cyclosporine at 10:00 a.m. and 10:00 p.m. The blood concentration data were subjected to simultaneous computer nonlinear least squares regression analysis using a 1-compartment pharmacokinetic model. The blood concentrations of cyclosporine at 10:00 a. m. were increased significantly during 2-6 hr compared to those at 10:00 p.m. The area under the blood concentration-time curve (AUC) and peak concentration $(C_{max})$ of cyclosporine at 10:00 a.m. were increased significantly compared to those at 10:00 p.m. The mean total body clearance (CL) of cyclosporine at 10:00 a.m. were decreased significantly compared to those at 10:00 p.m. It is reasonable to consider individual circadian rhythm for effective dosage regimen of cyclosporine in therapeutics.

• Archives of Pharmacal Research
• /
• v.20 no.6
• /
• pp.629-632
• /
• 1997

The pharmacokinetics of YH439 and its metabolites were investigated after oral administration of YH439 to rats to investigate the food effect. After oral administration of YH439, its metabolites, M4 and M5 were detected in plasma. YH439 was not detected in the plasma for both fasted and fed rats for all doses studied. The pharmacokinetic parameters of the metabolites were not affected by food at all doses studied. The results of this study indicated that there are no significant food effects on the pharmacokinetics of YH439 and its metabolites in rats.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.2
• /
• pp.89-94
• /
• 2001

The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.